1. Field of the Invention
Embodiments of the invention generally pertain to agonists and antagonists of LDCAM, as well as methods of treating disease by administering one or more LDCAM antagonists or agonists.
2. Description of Related Art
LDCAM is a homophilic cell adhesion molecule that has been shown to modulate T-cell function by interacting with one or more T-cell surface molecules thereby causing alteration of cellular signaling. LDCAM was shown to self-associate to form a homodimer and bind to B7L-1. LDCAM was also shown to generate increases in natural killer cell populations. U.S. patent application Ser. No. 09/778,187, filed Feb. 6, 2001, describes LDCAM and is incorporated herein by reference in its entirety.
LDCAM is also referred to in the art as Igsf4, TSLC1, SynCAM and Nectin-Like-2 and has been characterized as a member of the Nectin-like family of immunoglobulin-like cell surface receptors and as having three C2 Ig-like domains. The cytoplasmic tail of Nectin-like receptors has a band-4.1 protein binding site and a PDZ-protein binding site. LDCAM has been identified as a tumor suppressor gene deleted in non-small cell lung carcinoma and having homology to NCAM (Gomyo et al. Genomics 62:139-146 (1999) and Kuramochi et al. Nat Genet 27(4):427-30 (2001) Masuda et al. J Biol Chem. 277(34):31014-9 (2002)).
As described herein, it has been discovered that LDCAM binds to CRTAM. CRTAM has been described as a member of a family of cell surface markers initially designated as a class I-restricted T cell-associated molecule (CRTAM) as a result of its restricted expression pattern in T cells (U.S. Pat. No. 5,686,257). cDNA library subtraction techniques showed that mRNA transcripts were expressed by activated mouse alphabetaTCR+ CD4-CD8-(double-negative) T cells, a subset of natural killer T (NKT) cells. Human CRTAM has also been identified, and shares the same expression pattern as the mouse molecule. LPTN and CRTAM exhibit the same expression pattern in T cells, suggesting the existence of a gene expression program common to class I-MHC-restricted T cells (Kennedy, et al., J Leuk Bio 67, 725 (2000)).